HOBOE: A Phase 3 Study of Adjuvant Triptorelin and Tamoxifen, Letrozole, or Letrozole and Zoledronic Acid in Premenopausal Patients With Breast Cancer.

NCT00412022 | Unknown Phase 3

• 1 other identifier: HOBOE
• Study Type: interventional
• Target: 1,294
• Locations: 1 country
• Sites: 20

Brief Summary

The HOBOE study was amended in November 2009, and, after reaching enrollment of the first 500 patients, the study began recruiting premenopausal patients only. The primary objective of the extended study is to compare disease free survival in premenopausal patients with early breast cancer. Patients receive triptorelin and are randomized in a 1:1:1 fashion to receive tamoxifen or letrozole, or letrozole + zoledronic acid. The purpose of the HOBOE study, Version 1, was to compare the adjuvant hormonal therapy treatments of Tamoxifen, Letrozole and Letrozole + Zoledronate for their effects on bone loss in breast cancer patients. Postmenopausal and premenopausal patients were eligible, the latter also receiving monthly triptorelin. Upon reaching the enrollment of the first 500 patients in March 2010, the study began recruiting premenopausal patients only.

Conditions

Breast Cancer

Keywords

early breast cancer; adjuvant therapy; premenopause; premenopausal; menopausal status; postmenopause; bone mineral density; hormone sensitive; aromatase inhibitors; letrozole; disease-free survival

Outcome Measures

Primary Outcomes (2)

• disease free survival in premenopausal patients

  observation period is 10 years from initiation of treatment

• bone mineral density

  12 months from initiation of therapy

Secondary Outcomes (4)

• Bone mineral density measured

  yearly after first year of therapy

• disease free survival in postmenopausal patients

  observation period is 10 years from initiation of treatment

• overall survival

  observation period is 10 years from initiation of treatment

• toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patients

  monthly

Study Arms (3)

A

ACTIVE COMPARATOR

Triptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years

Drug: tamoxifen; Drug: triptorelin

B

ACTIVE COMPARATOR

Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years

Drug: triptorelin; Drug: letrozole

C

EXPERIMENTAL

Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily for 5 years + zoledronic acid 4 mg every 6 months.

Drug: triptorelin; Drug: letrozole; Drug: zoledronic acid

Interventions

tamoxifen DRUG

20 mg daily for 5 years

A

triptorelin DRUG

Premenopausal patients will receive triptorelin 3.75 mg IM at the beginning of therapy and every 4 weeks for 5 years or up to age 55

A; B; C

letrozole DRUG

2.5 mg daily for 5 years

B; C

zoledronic acid DRUG

4 mg every 6 months

C

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological diagnosis of breast cancer
• Surgical resection of breast cancer (breast conserving surgery or mastectomy)
• No evidence of disease
• Indication for adjuvant hormonal therapy (ER and/or PgR positive with IHC exam in at least 1% of primary tumor cells, according to St. Gallen criteria)
• Patient age at least 18 years
• Written informed consent . Premenopausal status defined as LMP within 12 months of randomization (FSH, LH will not be considered as determinants of menopausal status due the chemotherapy induced reversible ovarian suppression)
• Please note that patients who have received neoadjuvant or adjuvant chemotherapy and/or locoregional radiation therapy may be included in the study

You may not qualify if:

• Performance status (ECOG)\>2.
• Previous or concomitant malignancy (with the exception of adequately treated nonmalignant skin cancer and carcinoma in situ of the uterine cervix
• Metastatic breast cancer
• Creatinine \> 1.25 times the value of upper normal limit
• Pregnant or lactating females
• Clinical or radiologic evidence of bone fractures
• Treatment with systemic cortisone therapy within 12 months prior to randomization
• Treatment with drugs that could alter bone metabolism (calcitonin, mithramycin, gallium nitrate) within 2 weeks prior to randomization
• Previous treatment with tamoxifen or aromatase inhibitors
• AST and/or ALT \> 3 times the value of upper normal limit with clinical and laboratory findings that indicate a grade of hepatic insufficiency that could potentially increase the risk of assuming letrozole
• Any concomitant conditions that would, in the Investigator's opinion, contraindicate the use of any of the drugs used in this study
• Inability to provide informed consent
• Inability to comply with followup
• Patient undergoing invasive dental work at time of baseline evaluation or foreseen during the course of adjuvant therapy

Sponsors & Collaborators

• National Cancer Institute, Naples: lead
• University of Campania Luigi Vanvitelli: collaborator

Study Sites (20)

S. Giuseppe Moscati

Avellino, AV, Italy

Location

Azienda Ospedaliera Treviglio - Caravaggio

Treviglio, BG, Italy

Location

Azienda Ospedaliera G. Rummo

Benevento, BN, Italy

Location

Ospedale Senatore Antonio Perrino

Brindisi, BR, Italy

Location

Istituto Romagnolo per lo Studio e la Cura dei Tumori

Meldola, FC, Italy

Location

Presidio Ospedaliero Di Saronno Aziendo Ospedaliera di Busto Arsizio

Saronno, VA, Italy

Location

Ospedale Santa Maria Annunziata

Bagno a Ripoli, Italy

Location

Istituto Nazionale per la ricerca Sul Cancro

Genova, Italy

Location

Ospedale Riuniti

Livorno, Italy

Location

Ospedale Unico della Versilia

Lucca, Italy

Location

Istituto Nazionale dei Tumori,

Napoli, Italy

Location

Ospedale Cardarelli

Napoli, Italy

Location

Seconda Università di Napoli

Napoli, Italy

Location

Università Federico II, Cattedra di Oncologia Medica

Napoli, Italy

Location

Casa di Cura La Maddalena

Palermo, Italy

Location

Ospedale Silvestrini

Perugia, Italy

Location

Ospedale Santa Chiara

Pisa, Italy

Location

Università di Sassari

Sassari, Italy

Location

Ospedale Santa Chiara

Trento, Italy

Location

ASL Viterbo Ospedale Belcolle

Viterbo, Italy

Location

Related Publications (6)

• Rossi E, Morabito A, Di Rella F, Esposito G, Gravina A, Labonia V, Landi G, Nuzzo F, Pacilio C, De Maio E, Di Maio M, Piccirillo MC, De Feo G, D'Aiuto G, Botti G, Chiodini P, Gallo C, Perrone F, de Matteis A. Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial. J Clin Oncol. 2009 Jul 1;27(19):3192-7. doi: 10.1200/JCO.2008.18.6213. Epub 2009 Apr 20.

  PMID: 19380451 RESULT

• Rossi E, Morabito A, De Maio E, Di Rella F, Esposito G, Gravina A, Labonia V, Landi G, Nuzzo F, Pacilio C, Piccirillo MC, D'Aiuto G, D'Aiuto M, Rinaldo M, Botti G, Gallo C, Perrone F, de Matteis A. Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen + triptorelin in premenopausal patients with early breast cancer. J Clin Oncol. 2008 Jan 10;26(2):264-70. doi: 10.1200/JCO.2007.13.5319. Epub 2007 Dec 17.

  PMID: 18086795 RESULT

• Nuzzo F, Gallo C, Lastoria S, Di Maio M, Piccirillo MC, Gravina A, Landi G, Rossi E, Pacilio C, Labonia V, Di Rella F, Bartiromo A, Buonfanti G, De Feo G, Esposito G, D'Aniello R, Maiolino P, Signoriello S, De Maio E, Tinessa V, Colantuoni G, De Laurentiis M, D'Aiuto M, Di Bonito M, Botti G, Giordano P, Daniele G, Morabito A, Normanno N, de Matteis A, Perrone F. Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study. Ann Oncol. 2012 Aug;23(8):2027-2033. doi: 10.1093/annonc/mdr600. Epub 2012 Mar 12.

  PMID: 22412041 RESULT

• Gravina A, Gargiulo P, De Laurentiis M, Arenare L, De Placido S, Orditura M, Cinieri S, Riccardi F, Ribecco AS, Putzu C, Del Mastro L, Rossi E, Ciardiello F, Di Rella F, Nuzzo F, Pacilio C, Caputo R, Cianniello D, Forestieri V, Giuliano M, Arpino G, Orlando L, Mocerino C, Schettino C, Piccirillo MC, Gallo C, Perrone F. Ten-year update of HOBOE phase III trial comparing triptorelin plus either tamoxifen or letrozole or zoledronic acid + letrozole in premenopausal hormone receptor-positive early breast cancer patients. ESMO Open. 2025 Jan;10(1):104085. doi: 10.1016/j.esmoop.2024.104085. Epub 2025 Jan 3.

  PMID: 39754976 DERIVED

• Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

  PMID: 38979716 DERIVED

• Perrone F, De Laurentiis M, De Placido S, Orditura M, Cinieri S, Riccardi F, Ribecco AS, Putzu C, Del Mastro L, Rossi E, Tinessa V, Mosconi AM, Nuzzo F, Di Rella F, Gravina A, Iodice G, Landi G, Pacilio C, Forestieri V, Lauria R, Fabbri A, Ibrahim T, De Maio E, Barni S, Gori S, Simeon V, Arenare L, Daniele G, Piccirillo MC, Normanno N, de Matteis A, Gallo C. Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer: HOBOE phase 3 randomised trial. Eur J Cancer. 2019 Sep;118:178-186. doi: 10.1016/j.ejca.2019.05.004. Epub 2019 Jun 1.

  PMID: 31164265 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Tamoxifen; Triptorelin Pamoate; Letrozole; Zoledronic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Imidazoles

Study Officials

• Andrea De Matteis, M.D.

  NCI Naples, Division of Medical Oncology C

  PRINCIPAL INVESTIGATOR

• Ciro Gallo, M.D., Ph.D.

  University of Campania Luigi Vanvitelli

  PRINCIPAL INVESTIGATOR

• Francesco Perrone, M.D., Ph.D.

  NCI Naples, Clinical Trials Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2006
• First Posted: December 15, 2006
• Study Start: March 1, 2004
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: March 24, 2023

Record last verified: 2023-03

Locations

IT (20)